To improve my chemistry, i revisit some synthetic route seen in literature, only on paper with a small bibliographic study to check the feasibility of some hypothesis, with chemical and process optimization for industrialization.
In the search field below, type a reactions class (ex: alkylation) or name (ex: Lossen rearrangement) to find the message containing the link to the report which use the desired reaction. Also, references are clickable in reports.

I didn’t find any
publication about a synthetic route for this molecule, but i didn’t make a deep
search. So i decided on paper to elaborate from scratch a total synthesis in a
batch mode with the goal of industrial scale exploitation, with starting
materials as cheap as possible, and the simpler chemistry as possible.

There is always
numerous way which lead to the targeted molecule, this proposal is one among
others.

I think the building
block (5: indole) and (11: cyclopropyl phenyl carboxylic acid derivative) could
be manufactured by a third party, and the convergence by flow chemistry with
the constraint of absence of suspension (which is not the case in this
proposal) to avoids a clogging of the installation.

Total steps: 15 with 10 isolations

Update (i have finally found a document describing the route)

I
have finally found the patent (CA2796642A1), here the original route
with 15 steps. I prefer my version about the indol part synthesis
because it is not necessary to make a cross-coupling, or use a Grignard,
perchlorate and dihydrogen. This is globally the same numbers of steps
(7) and starting materials cost is similar.

About the
cyclopropyl moiety, their starting materials for the two versions (only
one showed) are expensive, it would be better to use the benzodioxole
and make the bromination (2nd version not showed, 1 step shorter). My
version is very explorative with the lactone opening, also the
cross-coupling method must be tested (i have seen in a publication an
analog of (8) without the Cl, cross-coupled by a Pd catalyst, so the
cross-coupling is probably tolerated by (8)).Update:
Added an optimized route for the alternate route access to the cyclopropyl moiety, shortening the synthesis by 2 steps.

Original route published by Vertex (15 steps)

Complete proposal hereDisclaimer:This is some personal works on paper only, i
have no responsibility in any way if somebody would try this route and has all
sort of troubles, including but not limited to: injuries and money loss. This
is for experienced chemists only, and tests must be conducted in a suitable lab
only.

But if my work is used
to synthesize the targeted molecule described here, please, send a word, even
if it fails, chemistry is always an experimental science. This will make me
pleased, thank you.